Noncovalent interactions: defining cooperativity. Ligand binding aided by reduced dynamic behavior of receptors. Binding of bacterial cell wall analogues to ristocetin A.

Changes in the relative populations of the monomer and asymmetric dimer forms of ristocetin A, upon binding of two molecules of ligand, suggest that ligand binding is negatively cooperative with respect to dimerization. However, strong hydrogen bonds formed in the binding sites of the ligands are reinforced in the dimer relative to the monomer, and the barrier to dissociation of the dimer is increased upon binding of the ligands. It is concluded that the interactions which are common in the binding of both ligands are made with positive cooperativity with respect to those involved in dimerization.

Kinetic barriers and ordering of non-covalently bound states.

Binding of a dimer of a glycopeptide antibiotic to two molecules of a ligand that are bound to a membrane surface (by a hydrocarbon anchor) has been investigated. This binding on a surface is cooperatively enhanced (surface enhancement) relative to the binding in solution, because the former occurs intramolecularly on a template. Previously a correlation between surface enhancement and thermodynamic stability of the dimer in free solution (Kdimsol) was hypothesised.

Changes in motion vs. bonding in positively vs. negatively cooperative interactions.

From a consideration of the interactions between non-covalent bonds, it is concluded that positively cooperative binding will occur with a benefit in enthalpy and a cost in entropy, and that negatively cooperative binding will occur with a cost in enthalpy and a benefit in entropy; experimental data support these conclusions.

Cooperative binding interactions of glycopeptide antibiotics.

Glycopeptide antibiotics of the vancomycin group bind to bacterial cell wall analogue precursors, and typically also form dimers. We have studied the interplay between these two sets of noncovalent bonds formed at separate interfaces. Indole-2-carboxylic acid (L) forms a set of hydrogen bonds to the glycopeptide antibiotic chloroeremomycin (CE) that are analogous to those formed by N-Ac-D-Ala.